This study approaches the problem of chemical carcinogenesis in the colon by study of the metabolism of possible carcinogens in this disease. The study focuses on enzymes involved in metabolism of the carcinogens. The hypothesis on which the work is based is that the carcinogen is converted enzymatically to an active, or proximate form. Persons with greater amounts of the enzyme would thus be more susceptible to the chemically induced tumor. Assays have been developed or are in the process of development for a number of carcinogen metabolizing enzymes in human tissues. Most work thus far is on aryl hydrocarbon hydroxylase (AHH), with an assay based on the use of short- term cultured lymphocytes. We have shown genetic variation in man for this enzyme, and are now in the process of determining whether there is relationship between activity of the enzyme and occurrence of colon cancer. Other enzyme systems will be similarly studied in subjects with carcinoma of the colon.